(1R*,3′S*,4′R*)-4′-(4-Chloro­phen­yl)-3′-[(4-hy­droxy-2-oxo-1,2-dihydro­quinolin-3-yl)carbon­yl]-1′-methyl­spiro­[ace­naphthyl­ene-1,2′-pyrrolidin]-2-one

The title compound, C32H23ClN2O4, has a quinoline, a chloro­phenyl and an acenaphthalene ring system attached to a central pyrrolidine ring, which has three stereogenic centers. Nevertheless, the compound crystallizes as a racemate with two mol­ecules of identical chirality in the asymmetric unit. They differ in the conformation of the five-membered pyrrolidine ring; in one molecule it has an envelope conformation, while in the other molecule it has a twisted conformation. In each molecule there is an intra­molecular O—H⋯O hydrogen bond making an S(6) ring motif. In the crystal, pairs of N—H⋯O hydrogen bonds produce inversion dimers with R 2 2(8) motifs. There are also C—H⋯O interactions present. The crystal structure contains voids (60 Å3) within which there is no evidence of solvent mol­ecules

Parental perceptions of the impact of neonatal unit visitation policies during COVID-19 pandemic

Objectives To ascertain parental perceptions of the impact of restricted visiting policies to neonatal intensive care units during the current COVID-19 pandemic. Design Cross-sectional survey of parents impacted by visitation policies. Setting Six tertiary level neonatal units, four from the UK and two from the USA, participated in the study. Participants Parents and families of infants hospitalised in the participating centres between 1 May 2020 and 21 August 2020. Methods Online-based and/or paper-based survey, querying the visitation policies and their impact on parents' ability to visit, care for and bond with their infants. Results A total of 231 responses were received. Visitation limited to a single visitor with no restrictions on duration was the most frequently reported policy; 140/217 (63%). Visitation policies were perceived as being restrictive by 62% (138/219) of the respondents with 37% (80/216) reporting being able to visit less often than desired, 41% (78/191) reporting being unable to bond enough and 27% (51/191) reporting not being able to participate in their baby's daily care. Mild to severe impact on breast feeding was reported by 36% (75/209) of respondents. Stricter policies had a higher impact on families and were significantly associated with a lack of bonding time, inability to participate in care and an adverse impact on breast feeding. Conclusions Visitation policies during the COVID-19 pandemic varied between centres and over time with stricter restrictions implemented earlier on in the pandemic. Parents reported significant impacts on their ability to visit, care for and bond with their infants with perceived severity of impact worse with stricter restrictions

Exclusively breastmilk‐fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

Background: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. Objectives: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively. Patients/Methods: Prospective, multi-center, observational study in preterm infants born <33 weeks’ gestation. Blood samples and dietary history were collected before hospital discharge, and post discharge at 2-3 months corrected age. Outcome measures were serum VK1, PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants post-discharge. Results: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies. Conclusions: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency

Neuronal let-7b-5p acts through the Hippo-YAP pathway in neonatal encephalopathy

Despite increasing knowledge on microRNAs, their role in the pathogenesis of neonatal encephalopathy remains to be elucidated. Herein, we identify let-7b-5p as a significant microRNA in neonates with moderate to severe encephalopathy from dried blood spots using next generation sequencing. Validation studies using Reverse Transcription and quantitative Polymerase Chain Reaction on 45 neonates showed that let-7b-5p expression was increased on day 1 in neonates with moderate to severe encephalopathy with unfavourable outcome when compared to those with mild encephalopathy. Mechanistic studies performed on glucose deprived cell cultures and the cerebral cortex of two animal models of perinatal brain injury, namely hypoxic-ischaemic and intrauterine inflammation models confirm that let-7b-5p is associated with the apoptotic Hippo pathway. Significant reduction in neuronal let-7b-5p expression corresponded with activated Hippo pathway, with increased neuronal/nuclear ratio of Yes Associated Protein (YAP) and increased neuronal cleaved caspase-3 expression in both animal models. Similar results were noted for let-7b-5p and YAP expression in glucose-deprived cell cultures. Reduced nuclear YAP with decreased intracellular let-7b-5p correlated with neuronal apoptosis in conditions of metabolic stress. This finding of the Hippo-YAP association with let-7b needs validation in larger cohorts to further our knowledge on let-7b-5p as a biomarker for neonatal encephalopathy

Endotracheal intubation in a neonatal population remains associated with a high risk of adverse events

Introduction: There has been a significant increase in premedication use for neonatal intubation in the UK over the past decade. We aimed to determine the adverse events during neonatal intubation using the most commonly used premedication regimen in the UK. Discussion: We prospectively studied all intubations performed using morphine, suxamethonium and atropine during a 3-month period in three UK tertiary neonatal units. Premedication was administered for 87/93 (94%) of intubations. Median time taken to prepare premedication was 16 min (IQR 10-35). Median time to successful intubation was 5 min (IQR 2-9) following premedication. Median lowest recorded oxygen saturation after administration of premedication was 65% (IQR 39-85). A bradycardia in the range 61-99/min accompanied the procedure in 24/93 (26%) intubations, with a median duration of bradycardia of 8 s (IQR 1-10). Conclusion: Despite the widespread move to premedication for neonatal intubation, many deficiencies in everyday practice remain. The rate of haemodynamic complications is high in this commonly used premedication regimen. This study shows that there are important factors to control at the local level in terms of timely preparation and administration of premedication drugs, training and supervision of staff carrying out this high-risk procedure